New vinyl-1,2,4-triazole derivatives as antimicrobial agents: Synthesis,biological evaluation and molecular docking studies |
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| Institution: | 1. Laboratory of Organic Synthesis and Biopharmaceuticals, Institute of Chemistry, Chisinau, 3 str. Academiei, Moldova;2. Scientific Center for Drug Research, “Nicolae Testemitanu” State University of Medicine and Pharmacy, Chisinau, Moldova;3. Department of Pharmacy School of Health, Department of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki 54124, Greece;4. Department of Plant Physiology, Institute for Biological Research “Sini?a Stankovi?” – National Institute of Republic of Serbia,University of Belgrade, Bulevar despota Stefana 142, 11000, Belgrade;5. Laboratory of Physical Methods of Solid State Investigation ″Tadeusz Malinowski, Institute of Applied Physics, Chisinau, 5 str. Academiei, Moldova;1. Chemistry Department, Faculty of Science, Suez Canal University, Ismailia, Egypt;2. Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt;3. Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt;4. Institute of Analytical Chemistry, Chemo and Biosensors, Universitätsstrasse 31, 93053 Regensburg, Germany;1. Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Aljouf, Saudi Arabia;2. Biochemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt;3. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Deraya University, Minia, Egypt;4. Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt;5. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt;1. Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University SubCampus, Osmanabad 413501, MS, India;2. Department of Pharmaceutical Chemistry, School of Pharmacy, Vishwakarma University, Pune 411048, MS, India;3. Department of Microbiology, Dr. Babasaheb Ambedkar Marathwada University SubCampus, Osmanabad 413501, MS, India;4. Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R. R. District, Hyderabad 500078, India;1. Department of Medicinal Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt;2. Department of Microbiology, Faculty of Pharmacy, October 6 University, 6 October City 12585, Giza, Egypt;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, October 6 University, 6 October City 12585, Giza, Egypt;1. Plant Protection College of Henan Agricultural University, Zhengzhou, 450002, China;2. Provincial Key Laboratory of the Discovery and Application of Novel Pesticide, Zhengzhou, 450002, China |
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| Abstract: | 1,2,4-Triazole is a very important scaffold in medicinal chemistry due to the wide spectrum of biological activities and mainly antifungal activity of 1,2,4-triazole derivatives. The main mechanism of antifungal action of the latter is inhibition of 14-alpha-demethylase enzyme (CYP51). The current study presents synthesis and evaluation of eight triazole derivatives for their antimicrobial activity. Docking studies to elucidate the mechanism of action were also performed. The designed compounds were synthesized using classical methods of organic synthesis. The in vivo evaluation of antimicrobial activity was performed by microdilution method. All tested compounds showed good antibacterial activity with MIC and MBC values ranging from 0.0002 to 0.0069 mM. Compound 2 h appeared to be the most active among all tested with MIC at 0.0002–0.0033 mM and MBC at 0.0004–0.0033 mM followed by compounds 2f and 2g. The most sensitive bacterium appeared to be Xanthomonas campestris while Erwinia amylovora was the most resistant. The evaluation of antifungal activity revealed that all compounds showed good antifungal activity with MIC values ranging from 0.02 mM to 0.52 mM and MFC from 0.03 mM to 0.52 mM better than reference drugs ketoconazole (MIC and MFC values at 0.28–1.88 mM and 0.38 mM to 2.82 mM respectively) and bifonazole (MIC and MFC values at 0.32–0.64 mM and 0.64–0.81 mM). The best antifungal activity is displayed by compound 2 h with MIC at 0.02–0.04 mM and MFC at 0.03–0.06 mM while compound 2a showed the lowest activity. The results showed that these compounds could be lead compounds in search for new potent antimicrobial agents. Docking studies confirmed experimental results. |
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| Keywords: | Vinyl triazole Lanosterol 14-alpha-demethylase Antifungal Antibacterial Sterol biosynthesis |
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